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O Svendsen

Publications and source records attributed to O Svendsen.

At least 19 recordsLinked to original sources
PubMed1992

Effect of immunosuppressive agents on the guanethidine-induced sympathectomy in athymic and euthymic rats.

Guanethidine sulphate causes destruction of peripheral sympathetic neurons and infiltration of mononuclear inflammatory cells in the sympathetic ganglia of both athymic nude (rnu/rnu) and euthymic LEW/Mol rats. The effect of guanethidine is believed to be an autoimmune reaction. To determine the effect of immunosuppressive drugs concurrently with guanethidine treatment both athymic and euthymic rats were treated with guanethidine 40 mg/kg i.p. daily for 14 days, cyclophosphamide 100 mg/kg i.p. on days 1 and 8, methylprednisolone 10 mg/kg and cyclosporin A 10 mg/kg daily from days 1 to 7, and then every other day from days 8 to 14. The number of neurons in the sympathetic ganglia was counted and four subpopulations of mononuclear inflammatory cells were identified by monoclonal antibodies MHC II, CD8 T-cells/NK-cells, CD5 T-cells, CD4 T-cells/macrophages. Our results show that the immunosuppressive drugs used were unable to prevent the guanethidine-induced reduction of sympathetic neurons, although the number, of neurons following guanethidine-methylprednisolone treatment was significantly higher compared with guanethidine alone in both athymic and euthymic rats. The identification of mononuclear cells in the sympathetic ganglia showed that the CD8/NK and CD5 populations were the populations primarily responding to guanethidine treatment. Both CD8/NK and CD5 populations were absent without guanethidine, but increased significantly following guanethidine in both athymic and euthymic animals. None of the immunosuppressive drugs used could prevent the guanethidine-induced rise in the CD8/NK population in neither athymic nor in euthymic rats. The rise in the CD5 population was suppressed following treatment with all immunosuppressive drugs in athymic rats, but only following methylprednisolone in euthymic animals. These results indicate that guanethidine induces proliferation of T-cells in euthymic rats and non-functional CD5 positive pre T-cells in athymic animals. The CD5 population in both athymic and euthymic animals appears relatively more sensitive to immunosuppressive drugs than the NK-cell population also activated by guanethidine. This relatively resistant NK-cell population seems to play an important role in the guanethidine-induced destruction of sympathetic neurons and can explain why the guanethidine-induced immunological reaction could not be fully prevented by the immunosuppressive drugs used. The conclusion is that guanethidine induces destruction of sympathetic neurons by a NK-cell-mediated reaction.

Animals↗
PubMed1992

Athymic experimental animals in pharmaco-immunological research.

Immunodeficient animals--the nude mouse and the nude rat--allow studies of drug action and possible side effects without interference from the immune system. Comparative investigations in athymic and euthymic animals allowed us to elucidate the role of T-lymphocytes in the pathogenesis of streptozotocin-induced diabetes mellitus in mice, and the importance of NK-cells as effectors in guanethidine-induced sympathectomy in the rat. It is suggested that immunodeficient animals should be included in toxicological studies of xenobiotics.

Animals↗
PubMed1992

Anti-asialo GM1 antibodies prevents guanethidine-induced sympathectomy in athymic rats.

Guanethidine sulphate induces destruction of peripheral sympathetic neurons and infiltration of mononuclear cells in rat sympathetic ganglia. The effect of guanethidine is believed to be an autoimmune reaction. In order to determine the effect of anti-asialo GM1, an antibody that binds to the glycolipid asialo GM1 expressed on rodent natural killer cells, athymic Lewis rats received guanethidine 40 mg/kg i.p. daily from day 1 to 14 and anti-asialo GM1 i.p. 1 mg/rat on day -2, 0, 2, 6, and 10 in the study period. Saline and anti-asialo GM1 were given alone in the same doses as control. The number of neurons in the sympathetic ganglia were counted and the ganglionic volume determined. The presence of natural killer cells in the ganglia were determined by immunohistochemical methods. Our results shows that anti-asialo GM1 can prevent guanethidine-induced reduction of sympathetic neurons, but not prevent the initiation of an immunological reaction in the ganglia. Natural killer cells could only be identified in ganglia following guanethidine treatment alone. It is concluded that anti-asialo GM1 treatment can prevent the guanethidine-induced sympathectomy by eliminating the natural killer cells from the ganglia.

Animals↗
PubMed1992

Rederivation of rat colonies seropositive for Bacillus piliformis and the subsequent screening for antibodies.

Latent infection of rats in a breeding colony with Bacillus piliformis detectable by antibodies to the agent in an immunofluorescence assay was eliminated by a combination of traditional rederivation techniques, using animal units not previously used for rat breeding, and the use of specific disinfection procedures. The success rate was apparently correlated with the use of peracetic acid instead of aldehyde products to decontaminate the animal unit.

Animal Husbandry↗
PubMed1991

Pretreatment with steroids before intravenous injection of diatrizoate or iohexol. Effects on urine and serum profiles.

The effects on urine and serum profiles of intravenous injection of diatrizoate, iohexol, or saline were studied in male rats pretreated with steroids or saline. Using urinary albumin, glucose, sodium, and the enzymes lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), and N-acetyl-beta-D-glucosaminidase (NAG) as markers of glomerular and tubular function, it was found that diatrizoate caused temporary glomerular and tubular dysfunction; the effect was independent of the kind of pretreatment. Iohexol did not cause increased glomerular permeability in steroid- and saline-pretreated rats. When used following saline, iohexol induced increased excretion of three tubular components, whereas iohexol plus steroids caused increased excretion of all five tubular components. The dysfunctional effect of iohexol plus steroids was less than that of diatrizoate plus steroids. The serum components revealed no abnormalities induced by either contrast media or methylprednisolone. Pretreatment with steroids has no effect on the glomerular or tubular dysfunctional effect of diatrizoate, whereas it worsens the temporary tubular dysfunctional effect of iohexol in rats.

Acetylglucosaminidase↗
PubMed1991

Effect of human growth hormone on the reproduction of female rats.

Female rats were treated with human growth hormone (hGH) 0.3, 1.0 and 3.3 IU/kg daily for two weeks before mating, throughout mating and during the first seven days of pregnancy. Treatment with 1.0 and 3.3 IU/kg hGH caused a significant prolongation of the oestrous cycle. As a consequence the number of mating days was more than doubled compared to placebo treatment. The number of implantation sites and corpora lutea was significantly higher in hGH treated rats than in placebo treated rats. The number of early resorptions was increased in the rats given 3.3 IU/kg. The number of foetuses in rats sacrificed on day 20 of pregnancy and the number of viable offspring from the rats allowed to give birth were significantly increased by treatment with 1.0 IU/kg hGH. In a study of 4-day cyclic rats, treatment with 3.3 IU/kg hGH caused a prolongation of the cycle length to an average of 10.1 days, and the plasma progesterone levels tended to be higher in those rats in which the cyclic patterns had been most deranged. Foetal body weights were increased in the hGH groups, and a study with 125I-hGH indicated that hGH administered to pregnant rats will to some extent pass the placenta.

Animals↗
PubMed1991

Muscle toxicity of diatrizoate and iohexol in rabbits. A model for local tissue damage.

The potential tissue irritating effect of diatrizoate and iohexol was studied by injecting the contrast media into the right longissimus dorsi muscle of rabbits. The left muscle served as control. The animals were sacrificed 3 days after the injection, at which time muscle tissue was examined for macroscopic changes and loss of the muscle enzyme creatine kinase (CK) from the injection site was determined. An irregular area of necrotic muscle tissue and a hemorrhage was found at the injection site in rabbits given diatrizoate, whereas iohexol only caused hemorrhage. The local loss of CK activity following diatrizoate (0.64 g muscle tissue) was statistically significantly greater than following iohexol (0.18 g muscle tissue). It is concluded that this model seems to be useful for identification of the irritating potential of contrast media. It is also concluded that diatrizoate caused more damage to the local muscle tissue than iohexol.

Animals↗
PubMed1990

Identification of the mononuclear cell infiltrate in the superior cervical ganglion of athymic nude and euthymic rats after guanethidine-induced sympathectomy.

Guanethidine sulphate 40 mg/kg intraperitoneally for 14 days induced chromatolysis and nerve cell death in the superior cervical ganglia of athymic nude (rnu/rnu) LEW/Mol rats and their euthymic (+/rnu) LEW/Mol heterozygous littermates. Histologically the sympathetic ganglia were dominated by an infiltration of small inflammatory cells. By means of monoclonal antibodies these cells were identified. The number of B-lymphocytes increased following guanethidine in both athymic and euthymic rats. The number of T-lymphocytes increased to a great extent in euthymic rats, but was virtually missing in athymic rats. The number of NK-cells and monocytes/macrophages increased in both athymic and euthymic rats. The conclusion is, that guanethidine exerts a direct effect on sympathetic ganglion cells followed by a thymus-independent immune response.

Animals↗
PubMed1990

Epidemiological studies of Bacillus piliformis infection and Tyzzer's disease in laboratory rats.

Characteristics in connection with the presence of Bacillus piliformis in the barrier-protected animal rooms of a breeding centre for laboratory rats are discussed. The incidence of antibodies against B. piliformis in IFA test is high -77.8% for the total breeding centre. Clinical and pathological changes are, however, rare and mainly connected with certain rat strains. Immunosuppression with prednisolone and subsequent histopathological tests of liver sections indicate that rats with MHC-type RT1.A-u have an increased risk of developing Tyzzer's disease, while RT1.A-1-carriers seem to be resistant to this disease.

Animals↗
PubMed1988

Biosynthetic human growth hormone: subchronic toxicity studies in rats and monkeys.

Biosynthetic human growth hormone was injected subcutaneously in rats for 90 days and in cynomolgus monkeys for 30 days. The daily doses were 0.5, 3.3 and 25 IU kg-1 (rats) and 0.3 and 15 IU kg-1 (monkeys). The growth hormone was tolerated well in both rats and monkeys. No drug related deaths occurred and all animals appeared to be normal and also behaved normally throughout the dosing period. Increased body weight gain, increased food utilisation and increased organ weights were seen in the rats in the high and intermediate dose groups. The higher doses of human growth hormone (3.3 and 25 IU kg-1) caused a glandular hyperplasia of the mammary gland in male and female rats with evidence of secretory activity. In the female monkeys secretory activity was seen without any sign of mammary gland hyperplasia. Mucification of the vaginal epithelium and stress induced prostatitis was observed in the rats. Additional treatment related changes in the rats were an increased haematopoietic activity in the spleen and an increase in the amounts of calcium and phosphate excreted in urine. An increase in fasting plasma glucose levels was seen in the male monkeys on the high dose level. The changes observed during the treatment periods presumably represent exaggerated pharmacological effects of the growth hormone.

Animals↗
PubMed1985

Pharmacological differentiation of dopamine D-1 and D-2 antagonists after single and repeated administration.

In single-dose experiments neuroleptics antagonize dopamine (DA)-agonist-induced stereotypies in animals. The antagonistic potency correlates with their clinical antipsychotic effects. In a series of experiments where DA-agonist-induced stereotyped gnawing in mice and rats was inhibited by neuroleptics it was shown that the antagonistic effect of butyrophenones was greatly attenuated by concomitant treatment with anticholinergics. The effect of phenothiazines was slightly attenuated and that of thioxanthenes and SCH 23390 remained unchanged. After repeated administration a differentiation is also seen in the ability of the antagonists to suppress DA-agonist-induced stereotypies. The differentiation in these experiments is similar to that seen in dopamine D-1 and D-2 receptor binding. The compounds can be classified into three pharmacological subgroups: butyrophenones (e.g., haloperidol) with affinity for D-2 receptors; phenothiazines (e.g., fluphenazine and perphenazine) with affinity for both D-2 and D-1 receptors but with preference for the D-2 receptors; and thioxanthenes (e.g., cis(Z)-flupentixol and cis(Z)-clopenthixol) with equal affinity for D-1 and D-2 receptors, and the selective D-1 antagonist SCH 23390. This compound has the same antistereotypic effect as is seen with the neuroleptics. We have also investigated the effect of the above-mentioned neuroleptics and SCH 23390 after 12 days' treatment and 3-5 days withdrawal. They were given either alone or in combination. When they were given alone a clear differentiation was seen between the groups when mice were tested for methylphenidate antagonism. The thioxanthenes and SCH 23390 retain their ability to antagonize the stereotyped gnawing; the phenothiazines show a reduced effect; and the butyrophenones have almost lost their ability to antagonize the stereotyped behavior.

Animals↗
PubMed1985

Down-regulation of dopamine D-2, 5-HT2 receptors and beta-adrenoceptors in rat brain after prolonged treatment with a new potential antidepressant, Lu 19-005.

Lu 19-005 is a new phenylindan derivative with strong and equipotent inhibitory effect on dopamine (DA), noradrenaline (NA) and serotonin (5-HT) uptake. The adaptive effects of 2 weeks treatment with Lu 19-005, on receptor binding in vitro and on d-amphetamine responsiveness in vivo have been investigated in rats. One or 3 days after the final dose the number of beta-adrenoceptors and of 5-HT2 and DA D-2 receptors was decreased by 20-30%, whereas alpha 1-adrenoceptor number was slightly decreased only 1 day after withdrawal. The DA D-2 receptor number remained decreased at 7 days withdrawal, but returned to normal after another 3 days. The brain levels of DA, NA and 5-HT were not changed by 2 weeks' Lu 19-005 treatment. The down-regulation of DA D-2 receptors was accompanied by tolerance to d-amphetamine-induced hypermotility (after low doses) and stereotyped licking or biting (after a high dose). The tolerance to d-amphetamine-induced hypermotility was maximal at 3-5 days withdrawal time, and remained significant also 15 days after the last dose. An acute dose of Lu 19-005 did not modify the effects of d-amphetamine. The results are discussed in relation to the effect of prolonged treatment with other antidepressant drugs.

Animals↗
PubMed1979

Long term effect of teflutixol on apomorphine-induced stereotypy and vomiting in dogs.

Dose--response relationships to apomorphine-induced vomiting and stereotyped running behaviour have been determined in dogs before, and up to 24 and 28 days respectively, after daily oral treatment with 2.5 mg/kg of teflutixol or 12 days. The ED50 values for apomorphine-induced vomiting after teflutixol were not different from those obtained before treatment. Stereotyped running behaviour of increasing intensity was seen 4--12 days after teflutixol treatment. The intensity then declined and returned to normal. The results suggest that the nigro-neostriatal dopamine system in dogs became hypersensitive after prolonged teflutixol treatment, while the dopamine receptors of the emetic chemotrigger zone did not.

Animals↗
PubMed1979

The loss of creatine phosphokinase (CK) from intramuscular injection sites in rabbits. A predictive tool for local toxicity.

The CK activity was measured in muscle tissue taken from the injected area (dorsal longissimus muscle) and the contralateral side of the injection site 72 hours after intramuscular injection into rabbits of 1 ml of different dilutions of propylene glycol or glycerol formal in distilled water or 0.9% saline. The total loss of CK activity from the injection site was calculated as the difference between the CK concentration in the normal muscle tissue and that of the injection site from the same animal. From the results the arbitrary amount of muscle tissue depleted of CK activity was further calculated and compared with the severity of the gross pathological findings. A large necrotic area at the injection site was present in all samples with more than 1 g of muscle tissue depleted of CK activity. Minor and probably acceptable pathological changes were found in samples with less than 1 g of muscle tissue depleted of CK activity. The local damaging effect of drug preparations for intramuscular use can thus be evaluated from the calculated amount of muscle tissue depleted of CK activity.

Animals↗
PubMed1978

Hepatotoxicity of citalopram in rats and first-pass metabolism.

A chronic oral toxicity study of citalopram in rats revealed dose dependent hepatic fatty infiltrations in male rats while female rats were unaffected. Subsequent studies demonstrated markedly reduced availability due to first-pass hepatic metabolism in male rats and roughly complete availability in females. Pretreatment of male rats with phenobarbital for 2 weeks caused increased metabolism and simultaneous administration of phenobarbital and citalopram gave more pronounced fatty infiltrations than citalopram alone. A connection is suggested between the first-pass metabolism in male rats and the hepatotoxicity, which is possibly mediated through a metabolite or intermediate formed in toxic amount during the first passage of the liver.

Administration, Oral↗